Recently, studies have been made of targeting therapy, wherein a monoclonal antibody specific to cancer cells is linked to a anticancer substance to focus the anticancer substance onto the cancer tissue using the specificity of the monoclonal antibody.
Although, as anticancer substances used in such an approach, a plant toxin ricin, diphtheria toxin and the like have been studied, the use of lymphotoxin as a anticancer substance for the targeting therapy has not been attempted.
As methods of linking a cancer-specific antibody and an anticancer substance wherein they are directly covalently linked, a method wherein a liposome encapsulating an anticancer substance is linked to a cancer-specific antibody, and the like, is known.
Nevertheless, an attempt wherein an affinity of protein A to an antibody is used to link a cancer-specific antibody and an anticancer substance for the targeting therapy has not been made.
Although it is already known to prepare a fused protein comprising protein A and a physiologically active peptide (WO 84/03103), this approach is mainly directed to an affinity purification of the physiologically active peptide and the preparation of an antigen for immunization.
A conventional approach wherein an anticancer substance is chemically linked to a cancer-specific antibody for the targeting therapy is disadvantageous in that it is difficult to make the anticancer substance enter cancer cells. Conversely, it is known that lymphotoxin selectively and directly kills cancer cells via receptors on a surface of the cancer cell. Accordingly, the present invention is intended to provide a means of an effective cancer therapy such as a targeting therapy using lymphotoxin having such an advantageous property.